Medical Management of Sleep Disturbance During Opioid Tapering

This study will evaluate whether a dual orexin-receptor antagonist approved by the FDA for sleep disturbance, suvorexant (SUVO; Belsomra), will increase total sleep time in patients with opioid use disorder (OUD) undergoing supervised withdrawal. This study is designed as a dose-finding study of SUVO compared to placebo. Briefly, OUD patients seeking supervised withdrawal will be admitted into a clinical research unit and stabilized onto buprenorphine for three days before being randomly assigned to study condition. All participants will then undergo a routine four-day buprenorphine taper, followed by a four-day post-taper phase. Participants will be randomized to receive either placebo, Low Dose SUVO, or High Dose SUVO and the investigators hypothesize that one or both doses of SUVO will improve total sleep time relative to placebo. Patients will attend a single follow-up session, 5-10 days following discharge.

Study Overview

• Status: Completed
• Conditions: Sleep Disturbance; Opioid Dependence; Opioid Withdrawal
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Low Dose Suvorexant; Drug: High Dose Suvorexant

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years old and above
• Meets Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for OUD with evidence of physical dependence on opioids, and seeking treatment to stop using illicit opioids.
• Provides a urine sample that tests positive for opioids.
• Willing to comply with the study protocol.
• Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation.

Exclusion Criteria:

• Seeking or currently enrolled in methadone or buprenorphine maintenance treatment for OUD
• Pregnant or breast feeding
• Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification
• Have a known allergy to the study medications
• Past 30-day prescribed use of suvorexant or benzodiazepines for the indication of insomnia
• Current use of a Selective Serotonin Reuptake Inhibitor (SSRI) or Monoamine oxidase (MAO) inhibitor for depression or insomnia, or other medications that are contraindicated with suvorexant
• Current narcolepsy, restless leg syndrome or sleep paralysis
• High risk for current sleep apnea
• Current major depressive disorder
• Past year suicidal behavior

• Severe hepatic or renal impairment

  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) >3x ULN
  • Total bilirubin >2x Upper Limit of Normal (ULN)
  • Creatinine >1.5x ULN
• Have circumstances that would interfere with study participation (e.g., impending jail)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo sleep medication (Placebo oral capsule)	Drug: Placebo oral capsule; Placebo Sleep Medication
Active Comparator: Low Dose Suvorexant; Low dose sleep medication	Drug: Low Dose Suvorexant; Low Dose Suvorexant
Active Comparator: High Dose Suvorexant; High dose sleep medication	Drug: High Dose Suvorexant; High Dose Suvorexant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Abuse Liability as Assessed by Visual Analogue Scale	Area-under-the-curve of self-reported feelings of drug "High" on the morning after study drug administration, measured each morning on a 0-100 point visual analogue scale of the question "Last night, did you feel HIGH?". A score of "0" indicates no abuse liability and a score of 100 indicates extreme abuse liability. This will be assessed over four nights during an opioid taper.	4 nights
Total Sleep Time During Buprenorphine Taper	Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy.	Four nights during a buprenorphine taper
Total Sleep Time During Post-taper	Area-under-the-curve scores of total number of minutes slept per night as measured by a 3-lead wireless electroencephalography and wrist worn actigraphy.	Four nights following buprenorphine discontinuation
Subjective Opiate Withdrawal Scale During Buprenorphine Taper	Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal).	Three days during a buprenorphine taper
Subjective Opiate Withdrawal Scale During Post-taper	Area-under-the-curve of peak daily scores on the Subjective Opiate Withdrawal Scale (SOWS) (a 16-item self-reported scale that measures individual opioid withdrawal symptoms using a 0-4 Likert scale; total range of SOWS is 0-64; lower scores indicate mild opioid withdrawal relative to higher scores which indicate more severe opioid withdrawal).	Three days following buprenorphine discontinuation

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Andrew S Huhn, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: December 26, 2018
• First Posted (Actual): December 28, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2022
• Last Update Submitted That Met QC Criteria: July 12, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Nervous System Diseases; Substance-Related Disorders; Sleep Wake Disorders; Narcotic-Related Disorders; Dyssomnias; Parasomnias; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: IRB00198426; UG3DA048734 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No